In 2006 Yale started the innovative Medical Research Scholars Program (MRSP) with the mission of providing broad and deep Ph.D. training in the core basic science concepts of molecular biology, cell biology, biochemistry, genetics, physiology, pharmacology, and pathology, integrated with intensive exposure to medically oriented coursework and mentored clinical experiences designed specifically for Ph.D. students. The ultimate goal of this training is to prepare our students to be future interdisciplinary leader in the biomedical sciences, with a unique ability to pursue clinically relevant fundamental basic science inquiry aimed at elucidating the molecular mechanisms of disease. The MRSP has been supported by a combination of institutional funds and funds provided by the Howard Hughes Medical Institute (HHMI). The combination of substantial unmet demand from highly qualified students for admission (warranting expansion of the size of MRSP), the termination of HHMI support after the 2013-2014 academic year, and the desire to continue this highly successful ongoing program constitute the rationale for our Molecular Medicine (MM) Training Grant application. MRSP students participate in a variety of program activities designed to engage Ph.D. students in medically relevant training and experiences throughout their graduate studies. The classes focus first on normal human physiology, organ-based cell biology, and biostatistics, followed by human pathobiology and an introduction to drug discovery, validation, and clinical trials. MRSP students also have the option to participate with first-year Yale MD students in weekly small-group physiology case conference tutorials, in which they explore in depth the physiological underpinnings of particular disease states. The cornerstone of the MRSP is a two-year mentored clinical experience that provides students with in-depth exposure to the science behind human diseases and first-hand longitudinal encounters with patients to contextualize the mechanistic basis of disease in a way that is not possible through traditional classroom learning. In addition, MRSP students participate in a special research-in-progress series held jointly with the Yale Center for Clinical Investigation (YCCI)-an NIH-funded center that forms the nucleus for translational and mechanistic disease-focused research at Yale-and as the program grows we plan to incorporate an Annual Retreat (also in conjunction with the YCCI). In addition to these formal activities, the MRSP also provides ongoing mentoring to all MRSP trainees regarding selection of a thesis research laboratory and assembly of the dissertation committee to support the goal of the NIGMS Molecular Medicine program to provide training in the basic biomedical sciences with a focus on elucidating the mechanisms of human disease. Accordingly, we request funds for this MM Training Grant to support a total of five MRSP Ph.D. students per class year, with five second-year and five third-year students being supported at any given time (all first-year students are fully supported by institutional funds), with the expectation that MRSP students will complete the Ph.D. within six years.